Method for chlorinating ketones

ABSTRACT

In a process for chlorinating ketones which, apart from the carbonyl group, are inert in respect of triarylphosphine dichlorides, except for cyclopropyl methyl ketone, in which the ketones are reacted with a chlorinating agent in the presence of triarylphosphine oxides, the amount of triarylphosphine oxide is from 0.1 to 10 mol %, based on the amount of ketone. The ketones preferably have a least one CH-acid proton in the α position to the carbonyl group.

The present invention relates to a process for chlorinating ketones, inparticular ketones which have at least one CH-acid proton in the αposition to the carbonyl group. Chlorination of these ketones formspredominantly chlorine-substituted alkenes.

Chlorinated alkenes are valuable intermediates for organic synthesis,since they can easily be functionalized further. Thus, for example,substituted alkynes are obtainable by elimination using bases.

Chlorinated alkenes can, for example, be prepared from ketones usingsuitable chlorinating agents. A particularly suitable chlorinating agentis PCl₅, phosphorus pentachloride. By means of phosphorus pentachloride,ketones can almost universally be converted into the correspondingchloroalkenes. However, as a starting material on an industrial scale,phosphorus pentachloride can only be handled with considerabledifficulty since it is a very hygroscopic, corrosive solid which givesoff hydrochloric acid fumes on contact with moisture. In addition,chlorination using phosphorus pentachloride is uneconomical since only 2of the 5 chlorine atoms are usable and it is an expensive startingmaterial.

Alternative reagents such as oxalyl chloride or triphenylphosphine incarbon tetrachloride are frequently usable only on a laboratory scale.The reaction of ketones in the presence of formamides as solvents leadsto formulation of the double bond at the same time as chlorination.

The chlorination of ketones and aldehydes using triphenylphosphinedichloride is also known. Liebigs Ann. 626 (1959), pages 28, 29, 32 and33 describe the synthesis of geminal dihalides from aldehydes andketones by reaction with triphenylphosphine dichloride. In the case ofketones having acidic protons in the α position, chlorinated alkenes areobtained. The triphenylphosphine dichloride is used in the reaction inequimolar amounts, based on the ketone.

The process has the disadvantage that the reaction has to be carried outin a suspension because of the sparing solubility of thetriphenylphosphine dichloride. On an industrial scale, this is oftenassociated with stirring difficulties. In addition, triphenylphosphinedichloride is highly corrosive and very hygroscopic, which makeshandling this compound difficult. Triphenylphosphine oxide is formed aswaste product and has to be disposed of.

U.S. Pat. No. 3,715,407 describes a process for chlorinating ketonesusing triphenylphosphine oxide. Here, triphenylphosphine oxide isreacted with phosgene to form triphenylphosphine dichloride which thenreacts with the keto group. This liberates carbon dioxide from thephosgene, as a result of which the reaction is driven in the directionof the products. According to U.S. Pat. No. 3,715,407, thetriphenylphosphine oxide is used in excess, preferably in a two-fold orgreater excess, based on the ketone. The use of these large amounts oftriphenylphosphine oxide makes the use of a suitable solvent necessary.In addition, the reaction again forms a large amount ofphosphorus-containing wastes which have to be disposed of.

DE-A-197 09 401, which has earlier priority but is not a priorpublication, discloses a process for halogenating cyclopropyl methylketone in which cyclopropyl methyl ketone is reacted withtriphenylphosphine dichloride which is prepared in situ by reaction oftriphenylphosphine oxide with phosgene. Here, the use of catalyticamounts of triphenylphosphine oxide is sufficient to enable the processto be carried out successfully.

It is an object of the present invention to provide a process forchlorinating ketones which avoids the disadvantages of the knownprocesses and can be applied to many different ketones.

We have found that this object is achieved by a process for chlorinatingketones which, apart from the carbonyl group, are inert in respect oftriarylphosphine dichlorides, except for cyclopropyl methyl ketone, inwhich the ketones are reacted with a chlorinating agent in the presenceof triarylphosphine oxides, wherein the amount of triarylphosphine oxideis from 0.1 to 10 mol %, based on the amount of ketone.

In the process of the present invention, a triarylphosphine oxide,preferably triphenylphosphine oxide, is added to the reaction mixture incatalytic amounts of from 0.1 to 10 mol %, preferably from 0.5 to 5 mol%, particularly preferably from 1 to 3 mol %, based on the amount ofketone. Passing phosgene continuously into the reaction mixture thenconverts the triphenylphosphine oxide into triphenylphosphinedichloride, the actual reactive species, with parallel formation ofcarbon dioxide.

According to the present invention, it has been found that the use ofonly catalytic amounts of triarylphosphine oxide is sufficient toachieve complete chlorination of many ketones. The use of catalyticamounts of triphenylphosphine oxide eliminates the need to use a solventfor the reaction. According to the present invention, the chlorinationis preferably carried out without solvents, which results in aconsiderable increase in the space-time yield. The triarylphosphineoxide can be dissolved in the ketone which is preferably converted intothe alkenyl chloride by chlorination, as long as the ketone is liquid atthe reaction temperature, preferably also at room temperature. In smallamounts as are used according to the present invention, thetriarylphosphine oxide is completely soluble in the ketone, as a resultof which deposits on parts of the plant or valve blockages are avoided.Another advantage is the significantly reduced amount ofphosphorus-containing reaction residue.

If the ketone is one which is solid at the reaction temperature, it ispossible to make use of solvents which are inert toward phosgene, forexample aromatic or aliphatic hydrocarbons such as toluene, xylene orchlorobenzene or else carboxylic esters such as ethyl acetate or cyclicethers such as dioxane or tetrahydrofuran.

The reaction temperature is preferably in the range from 70 to 200° C.,particularly preferably in the range from 80 to 150° C. The process canbe carried out batchwise or preferably continuously. The reactionproducts can be distilled from the reaction mixture or reactor outputand subsequently be further purified if necessary. The catalyst presentin the distillation residue is preferably returned to the reaction orcan be disposed of. The entire distillation residue can, according tothe present invention, be returned to the reaction.

According to the present invention, any suitable chlorinating agents canbe used. Examples of suitable chlorinating agents are phosgene, thionylchloride, oxalyl chloride, diphosgene and triphosgene. Preference isgiven to using phosgene since it is a very inexpensive and readilyavailable chlorinating agent which in the reaction forms only gaseousby-products which are simple to remove from the reaction mixture.

In the chlorination according to the present invention, it is possibleto use all ketones which, apart from the carbonyl group, are inert inrespect of triarylphosphine dichloride. Here, the use of cyclopropylmethyl ketone as described in DE-A-197 09 401, which has earlierpriority but is not a prior publication, is excluded from the scope ofthe present invention. The ketone can thus have any structure as long asonly the carbonyl group reacts with triarylphosphine chloride under thereaction conditions. The ketone should, for example, have no hydroxylgroups which react with the triarylphosphine dichloride under thereaction conditions.

The ketones used according to the present invention preferably have atleast one CH-acid proton in the a position to the carbonyl group. TheCH-acid proton is preferably present in the form of a methylene ormethine group. The ketone is preferably selected from among ketones ofthe formula I

R—C(O)—CH₂—R′  (I)

where R and R′ are, independently of one another, C₁-C₂₀-alkyl, whichmay be unbranched, branched or at least partly closed to form a cyclicsystem and may be interrupted by from 1 to 5 oxygen atoms, orC₆-C₁₈-aryl, where the alkyl radicals may be substituted by C₆-C₁₈-aryl,halogen or nitro and the aryl radicals may be substituted byC₁-C₂₀-alkyl, halogen or nitro, or R and R′ together form aC₁-C₂₀-alkylene group which may be substituted by C₁-C₂₀-alkyl,C₆-C₁₈-aryl, halogen or nitro and may be interrupted by from 1 to 5oxygen atoms, where 2 carbon atoms in the ring may be part of a furthercyclic aliphatic or aromatic system, with the exception of cyclopropylmethyl ketone.

The reaction of the ketones of the formula I generally gives a mixtureof the geminal dichloro compound R—C(Cl₂)—CH₂R′ and the stereoisomerchloroalkenyl compound of the formula R—C(Cl)═CH—R′.

The reaction generally leads predominantly to the chloroalkenylcompounds (chlorine-substituted alkenes). In the case of, for example,carbonyl compounds having two aromatic substituents, e.g. benzophenone,only the geminal dichloro compounds are formed in the chlorination.

The ketones used according to the present invention preferably have nohalogen or nitro substituents and are not interrupted by oxygen atoms.They are therefore preferably ketones which are, apart from the carbonylgroup, built up entirely of carbon and hydrogen. Particularlypreferably, R and R′ are, independently of one another, C₁-C₁₀-alkyl orC₆-C₁₂-aryl or together C₁-C₅-alkylene. In particular, R and R′ are,independently of one another, C₁-C₆-alkyl or phenyl or togetherC₂-C₄-alkylene. Examples of particularly preferred ketones areacetophenone, propiophenone, cyclohexanone, cyclopentanone, propanoneand dibutanone isomers, pentanone isomers, hexanone isomers, heptanoneisomers and octanone isomers. In particular, cyclopentanone orcyclohexanone is used in the reaction.

The invention is illustrated by the examples below.

EXAMPLES Example 1

The experiments were carried out in a standard 500 ml stirred apparatusfitted with gas inlet and a carbon dioxide condenser. 5.6 g oftriphenylphosphine oxide (0.02 mol) are dissolved in 78.4 g (0.8 mol) ofcyclohexanone. At from 100 to 120° C., a total of 82 g (0.82 mol) ofgaseous phosgene are passed in over a period of 6 hours. After strippingout the excess phosgene by means of nitrogen, the product (84.4 g) isfractionally distilled. 43.1 g (0.37 mol) of 1-chlorocyclohexene(content according to GC: >99% by area) go over at 35-37° C. at 17 mbar.

Example 2

5.6 g of triphenylphosphine oxide (0.02 mol) are dissolved in 91.4 g(0.8 mol) of 2-heptanone. At from 100 to 125° C., a total of 95 g ofphosgene (0.95 mol %) are passed in over a period of 7 hours. Strippingout the excess phosgene by means of nitrogen leaves 107.1 g of product.Fractional distillation under reduced pressure (42 mbar, 53-70° C.)gives 85 g of a mixture of the three isomeric chloroheptenes (cis- andtrans-2-chloro-2-heptene and 2-chloro-1-heptene) and2,2-dichloroheptane.

Example 3

5.6 g of triphenylphosphine oxide (0.02 mol) are dissolved in 96 g (0.8mol) of acetophenone. At from 80 to 120° C., a total of 90 g (0.9 mol)of gaseous phosgene are passed in over a period of 9 hours. Strippingout the excess phosgene by means of nitrogen leaves 110.6 g of product.According to GC, this still contains 6% of the starting materialtogether with 79% (87 g) of 1-phenylvinyl chloride and 2% (2.2 g) of1,1-dichlorophenylethane. Fractional distillation (0.3 mbar, 36° C.)gives 77.5 g of colorless liquid having a 1-phenylvinyl chloride contentof >90%.

We claim:
 1. A process for preparing alkenyl chlorides by chlorinatingketones which have at least one CH-acid proton in the α position to thecarbonyl group and which, apart from the carbonyl group, are inert inrespect of triarylphosphine dichlorides, except for cyclopropyl methylketone, in which the ketones are reacted with a chlorinating agent inthe presence of triarylphosphine oxide, the amount of triarylphosphineoxide being from 0.1 to 10 mol %, based on the amount of ketone.
 2. Aprocess as claimed in claim 1, wherein the ketones are selected fromamong ketones of the formula I R—C(O)—CH₂—R′  (I) where R and R′ are,independently of one another, C₁-C₂₀-alkyl, which may be unbranched,branched or at least partly closed to form a cyclic system and may beinterrupted by from 1 to 5 oxygen atoms, or C₆-C₁₈-aryl, where the alkylradicals may be substituted by C₆-C₁₈-aryl, halogen or nitro and thearyl radicals may be substituted by C₁-C₂₀-alkyl, halogen or nitro, or Rand R′ together form a C₁-C₂₀-alkylene group which may be substituted byC₁-C₂₀-alkyl, C₆-C₁₈-aryl, halogen or nitro and may be interrupted byfrom 1 to 5 oxygen atoms, where 2 carbon atoms in the ring may be partof a further cyclic aliphatic or aromatic system, and are chlorinated tochloroalkenyl compounds of the formula R—C(Cl)═CH—R′.
 3. A process asclaimed in claim 2, wherein R and R′ are, independently of one another,C₁-C₁₀-alkyl or C₆-C₁₂-aryl or together C₁-C₅-alkylene.
 4. A process asclaimed in claim 1, wherein the chlorinating agent used is phosgene. 5.A process as claimed in claim 1, wherein the triarylphosphine oxide usedis triphenylphosphine oxide.
 6. A process as claimed in claim 1, whereinthe chlorination is carried out in the absence of solvent.
 7. A processas claimed in claim 2, wherein the chlorination products obtained arepredominantly chlorine-substituted alkenes.
 8. A process as claimed inclaim 1, wherein the reaction products are removed from the reactionmixture by distillation and catalyst present in the residue is returnedto the reaction.